Objectives of this study are: 1) to correlate pulmonary removal of selected endogenous vasoactive hormones and lipophilic drugs with morphologically defined damage to the vascular endothelium, 2) to measure and compare "specific" binding of adrenergic receptor ligands in membrane and other subcellular fractions of lung with that in both the normal and injured, perfused organ. Removal of biogenic amines, prostaglandins, alpha and beta adrenergic blocking agents, imipramine and methadone will be measured by aplication of double indicator dilution techniques. A bolus of each substance (14C-labelled) along with high molecular weight 3H-dextran will be rapidly administered i.v. to anesthetized rabbits. For 25 seconds thereafter, aortic blood samples will be collected, the concentration of isotopes in each fraction measured, normalized and plotted as functions of time. Extraction (E) of the compound will be taken as the difference between its concentration and that of dextran in blood. Initially, (E) will be measured in relation to changes in the concentration of injected substances as well as pulmonary blood flow. In later studies, lung injury will be produced by hemorrhage, or administration of endotoxin, monocrotaline of alpha-naphthylthiorurea and similar measurements of (E) made. The degree and nature of injury will be assessed by electron microscopy. Thus, the magnitude and rate of change in (E) after initial injury, and correlation with morphological damage, will be determined. In membrane and other fractions of lung homogenates, "specific" binding of radioligands to adrenergic receptors will be measured and compared to that in paired, independently perfused rabbit lungs and with tissue obtained from human lung removed during surgery. These studies will reveal the role of altered metabolic function of endothelium in the pathogenesis of acute lung disease. Furthermore, the study will generate basic information on the ligand binding capacity of adrenergic receptors which are accessible from the pulmonary circulation, and their possible modification by lung injury.